Contrasting effects of afferent and efferent vagal nerve stimulation on insulin secretion and blood glucose regulation

Parasympathetic activation reduces hepatic glucose release and increases pancreatic insulin secretion in hyperglycemic conditions. Thus, vagal nerve stimulation (VNS) may potentially be effective in treating type II diabetes. To investigate this possibility, we hypothesized that VNS reduces blood glucose concentration [Glu] via insulin secretion. [Glu] together with insulin and glucagon serum concentrations were determined in anesthetized rats during baseline conditions and 120 min of cervical VNS with the nerve left intact for combined afferent and efferent VNS (n = 9) or the nerve sectioned proximal or distal from the stimulation electrode for selective efferent (n = 8) or afferent (n = 7) VNS, respectively. Afferent VNS caused a strong and sustained increase in [Glu] (+108.9 ± 20.9% or +77.6 ± 15.4%, after 120 min of combined afferent and efferent VNS or selective afferent VNS) that was not accompanied by an increase in serum insulin concentration. However, serum insulin levels increased significantly with selective efferent VNS (+71.2 ± 27.0% after 120 min of VNS) that increased [Glu] only temporarily (+28.8 ± 11.7% at 30 min of VNS). Efferent VNS initially increased serum glucagon concentration which remained elevated for 120 min when efferent VNS was combined with afferent VNS, but returned to baseline with selective efferent VNS. These findings demonstrate that afferent VNS causes a marked and sustained increase in [Glu] that is partly mediated by suppression of pancreatic insulin secretion. In contrast, efferent VNS stimulates pancreatic glucagon secretion that appears to be antagonized by insulin secretion in the case of selective efferent VNS. Selective efferent VNS may potentially be effective in treating type II diabetes.